Submissions for variant NM_003001.5(SDHC):c.118del (p.Arg40fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002342914	SCV002640404	pathogenic	Hereditary cancer-predisposing syndrome	2021-12-24	criteria provided, single submitter	clinical testing	The c.118delC pathogenic mutation, located in coding exon 3 of the SDHC gene, results from a deletion of one nucleotide at nucleotide position 118, causing a translational frameshift with a predicted alternate stop codon (p.R40Gfs*7). In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site; however, the impacted region is critical for protein function (Ambry internal data). This alteration has been observed in at least one individual with a personal and/or family history that is consistent with SDHC-related disease (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Myriad Genetics, Inc.	RCV003316865	SCV004018287	pathogenic	Paragangliomas 3	2023-03-17	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.