ClinVar Miner

Submissions for variant NM_015087.5(SPART):c.1110del (p.Lys370fs)

dbSNP: rs1060499524
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001008821 SCV001168623 pathogenic not provided 2018-08-21 criteria provided, single submitter clinical testing The c.1110delA variant in the SPG20 gene has been reported previously in the homozygous state in association with Troyer syndrome (Patel et al., 2002; Bakowska et al., 2008). The c.1110delA variant is considered a founder mutation in the Old Order Amish population (Patel et al., 2002). The c.1110delA pathogenic variant causes a frameshift starting with codon Lysine 370, changes this amino acid to an Asparagine residue and creates a premature Stop codon at position 30 of the new reading frame, denoted p.Lys370AsnfsX30. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Furthermore, the c.1110delA variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret c.1110delA as a pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV001008821 SCV001212740 pathogenic not provided 2023-07-08 criteria provided, single submitter clinical testing This premature translational stop signal has been observed in individuals with Troyer syndrome (PMID: 12134148, 18413476). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 3457). For these reasons, this variant has been classified as Pathogenic. This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change creates a premature translational stop signal (p.Lys370Asnfs*30) in the SPART gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SPART are known to be pathogenic (PMID: 18413476, 20437587, 20504295).
Revvity Omics, Revvity RCV000003621 SCV004238366 pathogenic Troyer syndrome 2023-03-22 criteria provided, single submitter clinical testing
OMIM RCV000003621 SCV000023784 pathogenic Troyer syndrome 2008-04-01 no assertion criteria provided literature only
PreventionGenetics, part of Exact Sciences RCV003904801 SCV004727602 pathogenic SPART-related disorder 2024-01-17 no assertion criteria provided clinical testing The SPART c.1110delA variant is predicted to result in a frameshift and premature protein termination (p.Lys370Asnfs*30). This variant was reported in the homozygous state in many Old Order Amish with Troyer syndrome (Patel et al 2002. PubMed ID: 12134148; Bakowska JC et al 2008. PubMed ID: 18413476). This variant is reported in 0.0015% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Frameshift variants in SPART are expected to be pathogenic. This variant is interpreted as pathogenic.

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