Submissions for variant NM_012434.5(SLC17A5):c.802_816del (p.Ser268_Asn272del)

dbSNP: rs386833994

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000485185	SCV000568752	pathogenic	not provided	2022-12-06	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In-frame deletion of 5 amino acids in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 15516337, 12121352, 15510212, 12359136, 21781115, 12794688, 10069709, 15805149, 10947946, 2334213, 16170568, 10581036)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000049971	SCV000699341	pathogenic	Salla disease	2017-05-12	criteria provided, single submitter	clinical testing	Variant summary: The SLC17A5 c.802_816del15 (p.Ser268_Asn272del) variant causes an in-frame deletion in the cytosolic loop between TM domains 6 and 7 (Aula_2000). This variant was found in 2/119968 control chromosomes at a frequency of 0.0000167, which does not exceed the estimated maximal expected allele frequency of a pathogenic SLC17A5 variant (0.0023717). Multiple publications cite the variant in affected homozygous and compound heterozygous individuals diagnosed with ISSD. Functional studies found that due to this variant the ISSD polypeptide is mainly constrained to the Golgi compartment with limited presence in the lysosomes (Aula_2002) and also that it abrogates the transport activity of sialin (Wreden_2016) In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic/likely pathogenic. Taken together, this variant is classified as pathogenic.
Baylor Genetics	RCV000049971	SCV001163088	pathogenic	Salla disease	2024-02-06	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000049971	SCV001198532	pathogenic	Salla disease	2023-12-31	criteria provided, single submitter	clinical testing	This variant, c.802_816del, results in the deletion of 5 amino acid(s) of the SLC17A5 protein (p.Ser268_Asn272del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs386833994, gnomAD 0.006%). This variant has been observed in individual(s) with severe infantile sialic acid storage disease (PMID: 10581036, 12794688, 15805149). This variant is also known as 801-815del, SSLRN deletion, or "the ISSD deletion". ClinVar contains an entry for this variant (Variation ID: 56558). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects SLC17A5 function (PMID: 12359136, 15510212). For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab	RCV000049971	SCV002027575	pathogenic	Salla disease	2021-09-05	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV005031539	SCV005672822	pathogenic	Sialic acid storage disease, severe infantile type; Salla disease	2024-03-14	criteria provided, single submitter	clinical testing
OMIM	RCV000005973	SCV000026155	pathogenic	Sialic acid storage disease, severe infantile type	2003-07-01	no assertion criteria provided	literature only
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)	RCV000049971	SCV000082380	probable-pathogenic	Salla disease		no assertion criteria provided	not provided	Converted during submission to Likely pathogenic.
OMIM	RCV000049971	SCV000240033	pathogenic	Salla disease	2003-07-01	no assertion criteria provided	literature only
Natera, Inc.	RCV000049971	SCV001453512	pathogenic	Salla disease	2020-09-16	no assertion criteria provided	clinical testing